DIAGNOSTIC ELECTRON MICROSCOPY AND PEDIATRIC PATHOLOGY

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The purpose of this protocol is to examine the toxicity and immuno- modulatory activity of GM-CSF and TNF in pts. with advanced cancer. The combination of GM-CSF and TNF stimulates the maturation of dendritic cells from CD34+ bone marrow progenitor cells in vitro. TNF has a two-fold function in the maturation of dendritic cells, it up-regulates the expression of the GM-CSF receptor on bone marrow progenitors and prevents their maturation into granulocytes. Dendritic cells are the most potent antigen presenting cells of the immune system. They function as initiators in organ transplant rejection, major histocompatibility restricted T cell responses and in the formation of antibodies dependent on T cells. Dendritic cells are found in small numbers in many tissues and in peripheral blood. This study will examine the activity of TNF and GM-CSF to stimulate the maturation and function of dendritic cells. Epidermal Langerhans cells were quantitated by S100 staining and peripheral blood mononuclear dendritic cell precursors by dendritic CFU assay in methy- cellulose. S100+ cells in the epidermis doubled after treatment (2.55 before treatment to 5.98 after treatment, p=0.029). Dendritic colony forming units in peripheral blood were increased after treatment in 3 patients with colorectal cancer but were not increased in pts. with melanoma. The major goal of this protocol is to determine whether the combination of GM-CSF and TNF causes maturation of dendritic cells and increases their number in the blood, bone marrow and skin and to determine if this increase produces tumor regressions.